Toxicology of Industrial Compounds

level, whilst humans are essentially insensitive (Hill et al., 1989; Grasso et
al., 1991).
Therefore, in contrast to rats, there is no conclusive evidence for a critical
role of TSH in thyroid stimulation and carcinogenesis in humans (Hill et
al., 1989). In cultured human thyroid cells, for example, THS was unable
to induce proliferation whereas a stimulation of growth was observed in
rat thyroid cells (Westermark et al., 1985). Clinical data are available for
some compounds such as the anticonvulsants phenobarbitone,
diphenylhydantoin and carbamazepine as well as the antibiotic rifampicin,
which are known liver microsomal enzyme inducers in man. They increase
thyroid hormone metabolism and excretion and eventually decrease serum
thyroid hormone levels. There is also evidence, that administration of these
drugs leads to thyroid stimulation, however, largely in the absence of
increased TSH levels (Curran and DeGroot, 1991). In addition,
epidemiological data are not in favour of a link between human use of such
compounds with an increased incidence of thyroid tumours (Curran and
DeGroot, 1991), nor have increased rates of thyroid cancers been reported
in areas of endemic iodine deficiency (McClain, 1989). Therefore, the
currently available data do not support the idea, that thyroid stimulation
as a response to chemically induced increases in circulating TSH
concentrations significantly contributes to thyroid tumour formation in
man.
Compound B has been shown to cause thyroid tumours in the rat. In a
series of speciality studies, the compound was identified as an enzyme
inducer and a 5′-deiodinase inhibitor in the rat liver. These findings argue
for a rodentspecific, indirect mechanism leading to the formation of thyroid
tumours. Moreover, the observed dose-response characteristics are
indicative of a threshold process, e.g. liver enzyme induction and inhibition
of 5′-deiodination are irrevocable prerequisities for thyroid tumour
formation in this species.
Benzotriazole-based light stabilisers
H.THOMAS ET AL. 323
Ester derivatives of the 3-[3-(2H-benzotriazole-2-yl)-5-tert-butyl-4hydroxy-phenyl]
propionic acid represent potent UV-light absorbers and
constitute an important class of industrial plastic additives and light
stabilisers (Compounds C-F, Table 23.1). Toxicologically, this class of
chemicals is characterised by generally low acute oral or dermal toxicity
and the lack of genotoxicity in the commonly employed battery of
bacterial and cellular mutagenicity tests. Irrespective of the alcohol moiety,
however, all compounds, when administered subchronically to rats,
displayed very similar predominantly hepatotrophic effects, with spleen and
kidney weights in addition being only slightly affected: pronounced
hepatomegaly, hepatocyte hypertrophy, and concomitantly increased